Martin-Bell Syndrome Causes, Risks and Treatment

Fragile X syndrome (also called Fragile X) is the most common inherited form of mental retardation.* It results from a change, or mutation, in a single gene, which can be passed from one generation to the next. Fragile X appears in families of every ethnic group and income level.

Symptoms of Fragile X syndrome occur because the mutated gene cannot produce enough of a protein that is needed by the body’s cells, especially cells in the brain, to develop and function normally.

The amount and usability of this protein, in part, determine how severe the effects of Fragile X are.

The most noticeable and consistent effect of Fragile X is on intelligence. More than 80 percent of males with Fragile X have an IQ (intelligence quotient) of 75 or less.1 The effect of Fragile X on intelligence is more variable in females.

Some females have mental impairment, some have learning disabilities, and some have a normal IQ.

People with Fragile X syndrome also share certain medical problems as well as many common physical characteristics,2 such as large ears and a long face.

In addition, having Fragile X is often associated with problems with sensation, emotion, and behavior.

The National Institute of Child Health and Human Development (NICHD), part of the National Institutes of Health (NIH), is a major sponsor of research on Fragile X syndrome.

Since 1991, when researchers funded by the NICHD discovered the gene that causes Fragile X, scientists have learned a great deal about that gene’s structure and functions.

The NICHD continues to support clinicians and scientists around the world who are working to find effective behavioral or other therapies, medical treatments, and prevention strategies for Fragile X.

What Causes Fragile X Syndrome?

Fragile X syndrome is caused by a defect in the FMR1 gene located on the X chromosome. The X chromosome is one of two types of sex chromosomes.

The other is the Y chromosome. Women have two X chromosomes while men have one X chromosome and one Y chromosome.

The defect (mutation) on the FMR1 gene prevents the gene from properly making a protein called the fragile X mental retardation 1 protein.

This protein plays a role in the functioning of the nervous system. The exact function of the protein is not fully understood. A lack or shortage of this protein causes the symptoms characteristic of fragile X syndrome.

What Are the Symptoms of Fragile X Syndrome?

Male patients usually have some level of intellectual disability. Female patients may have some intellectual disability or learning disability or both, but many women with fragile X syndrome will have normal intelligence.

These women might only be diagnosed with fragile X syndrome if another family member is also diagnosed.

People with fragile X syndrome may show a combination of the following signs as children and throughout life:

developmental delays, such as taking longer than normal to learn to sit, walk, or talk compared with other children of the same age

stuttering

intellectual and learning disabilities, such as having trouble learning new skills or information

anxiety (general or social)

autism

impulsiveness

attention problems

social problems, such as not making eye contact with other people, disliking being touched, and trouble understanding body language

hyperactivity

seizures

depression

difficulty sleeping

Some people with fragile X syndrome have facial or other physical abnormalities. These may include:

a large forehead or ears with a prominent jaw

an elongated face

protruding ears, forehead, and chin

loose or flexible joints

flat feet

What keeps the FMR1 gene from producing FMRP in Fragile X syndrome?

The information for making a protein has two parts: the introduction, and the instructions for the protein itself.

Scientists call the introduction “the promoter region” of the gene because of its role in starting the protein-building process.

(For a more complete description of how proteins are made and the parts of a cell involved in making a protein, see the Human cells 101 section.)

The promoter region of the FMR1 gene contains repeats of a specific sequence (cytosine-guanine-guanine or CGG-see the Human cells 101 section for specific information about the CGG sequence) that, when normal, controls the activity level of the gene in building FMRP.

The number of repeated sequences in the promoter region varies from person to person.

Most people who do not have Fragile X have between six and 40 CGG repeats,3 with the average being about 30 repeats in the promoter region.

The nucleus stores its genetic material in packages called chromosomes. Most people have 46 chromosomes in each cell-23 from their mother and 23 from their father.

After fertilization, the two sets of chromosomes match up to form 23 pairs. The chromosomes in the 23rd pair are called the sex chromosomes, X and Y; they determine a person’s sex. Males usually have one Y chromosome and one X chromosome; females usually have two X chromosomes.

Each chromosome is made up of genes. Genes contain the information used by other parts of the cell to make proteins, the body’s building blocks.

Proteins make up the structure of your organs and tissues; they are also needed for your body’s chemical functions.

Each protein performs a specific job in different types of cells, and the information for making at least one protein is contained in a single gene.

Human cells 101

More than 100 trillion cells make up the human body. Most of these cells contain all the genes and other information needed to “build” a human being.

Much of this genetic information is found in the nucleus of the cell, a “control center” that keeps all the material together in one place.

How many people are affected by Fragile X syndrome?

Currently, researchers don’t know exactly how many people have either the full mutation or the premutation form of the FMR1 gene.

Even though researchers can estimate the number of people affected by Fragile X, these estimates can be very different.*

The important thing to remember is that, when you consider the individuals affected by full mutation and premutation forms of the FMR1 gene, their families, and their communities, this condition impacts hundreds of thousands of people.

How is Fragile X syndrome inherited?

The gene for Fragile X is carried on the X chromosome. Because both males (XY) and females (XX) have at least one X chromosome, both can pass on the mutated gene to their children

How Is Fragile X Syndrome Diagnosed?

Children who show signs of developmental delays or other outward signs including a large head circumference, or subtle differences in facial features at a young age may be tested for fragile X syndrome.

Fragile X syndrome can be diagnosed using a DNA blood test called the FMR1 DNA Test. The test looks for changes in the FMR1 gene that are associated with fragile X syndrome.

How Is Fragile X Syndrome Treated?

Fragile X syndrome cannot be cured. Treatment is aimed at helping the patient learn key skills, such as language use and proper social interaction.

This may involve receiving extra help from teachers, therapists, family members, doctors, and coaches.

There may be services and other resources available in your community to help children learn important skills for proper development.

Contact the National Fragile X Foundation at 1-(800) 688-8765 for more information regarding specialized therapy and educational plans.

Medications that are typically prescribed for behavior disorders, such as attention deficit disorder (ADD) or anxiety, may also be prescribed to treat the symptoms of fragile X.

What Can Be Expected in the Long Term?

Fragile X syndrome is a life-long condition and can affect all aspects of life, including one’s schooling, work, and social life.

According to the Centers for Disease Control and Prevention (CDC), about 44 percent of women and nine percent of men with fragile X syndrome reach a high level of independence as adults.

The majority of women achieved at least a high school diploma and about half succeeded in holding a full-time job. (CDC)

However, the majority of men with fragile X syndrome require assistance with daily activities as adults. Few male patients achieve a high-school diploma or succeed in finding full-time work.